Field of the Invention
This invention relates to methods, materials and devices for bone and tissue augmentation, and in particular for the stabilization and/or correction of spinal compression fractures. The present invention also relates to radiopaque and non-radiopaque polymers, and their use in bone augmentation systems. Also described herein are novel vertebroplasty cements and delivery systems. The polymers and systems described herein can be used in methods for treating bone fractures, such as vertebral compression fractures.
Description of the Related Art
Polymeric materials are widely used in numerous applications. For example, therapeutic embolization is the selective blockage of blood vessels or diseased vascular structures. Examples of polymeric embolotherapy devices and reagents include embolic coils, gel foams, glues, and particulate polymeric embolic agents used, for example, to control bleeding, prevent blood loss prior to or during a surgical procedure, restrict or block blood supply to tumors and vascular malformations, e.g., for uterine fibroids, tumors (e.g., chemo-embolization), hemorrhage (e.g., during trauma with bleeding) and arteriovenous malformations, fistulas (e.g., AVF's) and aneurysms.
A number of technological applications involve the use of a polymer that undergoes a transition upon a change in temperature. For example, in the medical field, one way to introduce a solid polymer into a particular body region is to heat the polymer into a flowable state, then inject the polymer into the region and allow it to cool and solidify. U.S. Pat. No. 5,469,867 discloses side-chain crystallizable polymers that are said to be useful for occluding channels in a living mammal. Such polymers are said to be designed such that they can be melted so that they are flowable slightly above body temperature but solidify when cooled to body temperature. See also WO2004-014449, which describes a miscible blend of polymers for medical device applications. Each of these publications U.S. Pat. No. 5,469,867 and WO2004-014449 are incorporated herein by reference.
Vertebral Compression Fractures.
One of the most common types of bone fractures are vertebral compression fractures, with approximately 600,000 fractures diagnosed each year. A vertebral compression fracture comprises a collapse of one or more vertebrae in the spine, which, for example, may be caused by bone diseases such as osteoporosis or direct trauma to the spine. Several treatment options are available for such compression fractures. One non-invasive method of treating a compression fracture is by oral administration to the patient of the polypeptide calcitonin, which may provide an analgesic effect while treating the underlying fracture. However, such a relatively conservative treatment is typically not sufficient for patients with anything more than a modestly compromised vertebra.
Polymeric materials and application devices have also been developed for stabilizing and/or correcting the form of vertebral bodies that have been injured, such as by compression fractures occurring from trauma or as a result of osteoporosis or cancer. Such fractures, which may involve the compression or collapse of one or more vertebrae in the spine, cause pain and deformation of the spine via distortion of the normal approximately rectangular cross-section of the vertebral body.
Two minimally invasive surgical procedures are also available. For example, vertebroplasty is a medical procedure where bone cement is percutaneously injected into a fractured vertebra in order to stabilize it and reduce pain. Prior art minimally invasive vertebroplasty procedures typically use X-ray guidance to: (a) advance a hollow needle or cannula into a central volume of a vertebral body adjacent the fractured bone; (b) inject a precursor cement fluid (bone cement, e.g., polymethylmethacrylate-based cement, which may be referred to herein as PMMA); and (c) react the precursor fluid in situ with a catalyst and/or energy source so as to form a thermoset polymeric support/cement substance. Typically the precursor fluid includes a radio-opaque substance such as barium sulfate to permit X-ray visualization of the fluid as it is administered and/or after it has been cured. See for example, US Patent Application Publication Nos. 2009-0012525 (“Devices and systems for delivering bone fill material”); 2006-0142779 (“Cannula having asymmetrically-shaped threads”); and 2008-0154304 (“System and method for accessing a tissue structure”), each of which applications is incorporated by reference herein.
A variation of this treatment is known as kyphoplasty, a procedure to restore at least some of the height lost in vertebral compression fractures and to reduce spinal distortion. See for example Dublin, et al.; “The Vertebral Body Fracture in Osteoporosis: Restoration of Height Using Percutaneous Vertebroplasty”; AJNR Am J Neuroradiol 26:489-492, March 2005, which publication is incorporated by reference herein. In one example of kyphoplasty, a balloon may be first inserted through a needle into the fractured bone to restore the height and shape of the vertebra. Then the balloon is removed and the cement mixture is injected as described above into the cavity created by the balloon.
However, currently available techniques of both vertebroplasty and kyphoplasty have several drawbacks. Bone cements used in vertebroplasty and kyphoplasty that are on the market today are primarily based on PMMA. While PMMA is compatible with human tissue for this purpose, the polymer and its monomer may be non-ideal in many applications. For example, PMMA is not radiopaque and thus, for situations in which radiopacity is desired, e.g. to monitor its application into the human body, a radiopacifying agent is generally added to the polymer. Additionally, PMMA and its monomer are known to have a degree of inherent toxicity. Toxicity concerns limit the number of vertebral fractures that can be treated in a single procedure.
PMMA and other currently available bone cements are also prone to leakage into non-treatment areas due to the inability to accurately control their viscosity. Cement leakage into the spinal column can cause permanent paralysis or other neurological damage to the patient. The generally high viscosity of the currently available bone cements also tends to require that a larger, lower gauge needle be used during the surgical procedure, which may cause additional pain and trauma to the patient. Furthermore, after the bone cement hardens, the final rigidity of the hardened cement is generally about three times harder than that of the natural bone with which it interacts, making future vertebrae fractures more likely.
The currently available bone cements used in vertebroplasty and kyphoplasty systems are often provided as two or more distinct components, which require mixing in the operating room before injection into the fractured vertebra. One common mixture is a combination of PMMA, methyl methacrylate monomer, and a thermal-initiator. The step of mixing separate components can lead to technical problems in about 50% of the minimally invasive surgical procedures. For example, problems can arise with inconsistent mixing and limited working time for surgical application upon mixture. Therefore, there is a need to provide polymers and delivery systems for use in methods of treating compression fractures which overcome one or more of the above-discussed disadvantages.
Structural Alloplastic Bone Grafts and Spinal Fusion.
Another therapeutic application presenting structural challenges is alloplastic bone grafting. Bone grafting is used in repairs for a wide variety of medical conditions presenting the need to provide replacement of damaged, lost or diseased bone. In some applications, structural support during graft healing is provided by adjacent bone. However, in other applications the graft material provides support for tissue and body structure during the healing process. Bone grafts may employ naturally occurring bone materials (autografts, allografts and xenographs), or may employ synthetic materials (alloplatic grafts), or combinations of these.
Alloplastic graft materials are available that are flow-delivered, but typically, these have poor mechanical integrity and thus have generally been limited to non-structural applications. On the other hand, structural implants are available, but they typically require substantially invasive surgical procedures. In the case of spinal fusion procedures (e.g., interbody fusion), a structural support device made of plastic or titanium may be fixed between the vertebra to maintain spine alignment and disc height.
Although malleable or flowable alloplastic graft materials capable of forming in-situ structural elements have been proposed, these materials and methods have limitations due to the requirement for inconvenient in-situ curing or cross-linking steps, or due to the comparatively high temperatures required to render a conventional thermoplastic matrix material malleable or extrudable. See for example, US Patent Application Publication No. 2004-0230309 entitled “In-situ formed intervertebral fusion device and method”.
In addition to spinal fusion procedures, in the repair of vertebral compression fractures in youths to middle-age adults, it is desirable to avoid permanent implant or bone cement material in favor of the re-growth of natural bone to heal the fracture. In these patients, a structural alloplastic bone graft material suited to minimally invasive fracture repair is highly desirable.
For further information, see:    (a) Data Book on Mechanical Properties of Living Cells, Tissues, and Organs, Hiroyuki Abe (Editor), Kozaburo Hayashi (Editor), Masaaki Sato (Editor), Springer-Verlag, New York, Tokyo, 1996;    (b) Failure Strains Properties of the Whole Human Vertebral Body, Banse, X; Munting, E; Cornu, O; Van Tomme, J; and Delloye, C, Poster Session—The Spine—46th Annual Meeting, Orthopaedic Research Society, Mar. 12-15, 2000, Orlando, Fla.;    (c) Major bone defect treatment with an osteoconductive bone substitute. Paderni S, Terzi S, Amendola L., Chir Organi Mov. 2009 September; 93(2):89-96. Epub 2009 Jun. 16; and    (d) Cytokine Growth Factor Rev. 2009 October-December; 20(5-6):341-2. Epub 2009 Nov. 8. “Bone morphogenetic proteins (BMPs): from morphogens to metabologens”. Reddi A H, Reddi A.; each of these publications being incorporated by reference herein.